A Phase 1/2, Open-label Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmocodynamics and Preliminary Antitumor Activity of AT-1965 in Patients With Advanced, Refractory or Recurrent Solid Tumors

Alyssum Therapeutics7 sites in 1 country85 target enrollmentFebruary 13, 2024

ConditionsSolid Tumor

InterventionsAT-1965 Liposome Injection

DrugsAT-1965 Liposome Injection

Overview

Phase: Phase 1
Intervention: AT-1965 Liposome Injection
Conditions: Solid Tumor
Sponsor: Alyssum Therapeutics
Enrollment: 85
Locations: 7
Primary Endpoint: Dose Limiting Toxicity (DLT) according to CTCAE version 5.0 in Part A - Dose Escalation Phase
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a first-in-human, multicenter, open-label, dose escalation and dose expansion Phase 1/2 study to determine the MTD and/or the recommended Phase 2 dose (RP2D) and to characterize DLTs of AT-1965 as well as to investigate the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of AT-1965 in patients with advanced, refractory or recurrent solid tumors (nonresectable and/or metastatic) including mTNBC.

Registry

clinicaltrials.gov

Start Date

February 13, 2024

End Date

January 2027

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Alyssum Therapeutics

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•The patient has a histologically or cytologically confirmed unresectable or metastatic solid tumor that is refractory to standard therapy or for which in the opinion of the investigator no standard therapy is suitable.
•Patient should have at least 1 measurable lesion per RECIST version 1.1 as assessed by the investigator. For Part A only, patients with radiographically evaluable but non-measurable disease are allowed after discussion with the sponsor.
•Recovered from AEs (except irAEs) of prior chemotherapy (per NCI CTCAE version 5.0) to Grade ≤ 1 or return to baseline status (except for alopecia) as per Investigator's discretion.
•The patient has an ECOG performance status of 0 to
•The patient has adequate bone marrow, renal, and hepatic function, defined as follows:
•Hemoglobin ≥9.5 g/dL (without transfusion in the prior 3 weeks).
•Platelets ≥100 × 109 cells/L (may be achieved with transfusion as per PI discretion)
•ANC ≥1.5 ×109 cells/L (without the use of hematopoietic growth factors within 4 weeks prior to dosing).
•Creatinine Clearance ≥60 mL/min (by using Cockcroft-gault equation)
•Total bilirubin ≤1.5 × ULN, unless the patient has a prior history of Gilbert's syndrome, in which case ≤3.0 × ULN is acceptable.

Exclusion Criteria

•The patient has an uncontrolled or life-threatening, symptomatic, current or recurrent disease (e.g., cardiovascular, renal, hepatic, endocrine) or other abnormality that could affect the action, absorption, or disposition of the study drug, may impact the ability of the patient to participate, may affect clinical or laboratory assessments, or otherwise has the potential to confound the study results.
•Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function, unstable pulmonary condition) or any important medical or psychiatric illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study.
•Uncontrolled diabetes.
•Patients with a history of autoimmune disease. Excluded autoimmune conditions are listed in Appendix
•Patients with history of transient autoimmune manifestations of an acute infectious disease that resolved upon treatment of the infectious agent are not excluded (e.g. acute Lyme arthritis).
•Please contact the medical monitor regarding any uncertainty over autoimmune exclusions.
•History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on chest computed tomography scan in the last 6 months; NOTE: history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
•History of hemolysis or hemolytic anemia.
•Evidence of ongoing subclinical hemolysis (high LDH and low serum haptoglobin with increased reticulocyte count).
•History of adrenal gland disorders such as Cushing Syndrome, Congenital adrenal hyperplasia, Addison's Disease and hyperaldosteronism

Arms & Interventions

AT-1965 Liposome Injection

Intervention: AT-1965 Liposome Injection

Outcomes

Primary Outcomes

Dose Limiting Toxicity (DLT) according to CTCAE version 5.0 in Part A - Dose Escalation Phase

Time Frame: Dose limiting toxicities will be evaluated during the first treatment cycle (28 days)

Nature and frequency of dose-limiting toxicities (DLTs) associated with AT-1965 administration, maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D)

Objective Response Rate (ORR) based on RECIST version 1.1 in Part B - Dose Expansion Phase

Time Frame: 3, 6 and 9 month

Objective Response Rates (ORR) defined as proportion of patients with a best overall response of complete response (CR) or partial response (PR) according to RECISTv1.1 as assessed by the Investigator

Duration of Response (DoR) based on RECIST version 1.1 in Part B - Dose Expansion Phase

Time Frame: 3, 6 and 9 month

Duration of response (DoR) defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented according to RECIST v1.1 as assessed by the Investigator.

Secondary Outcomes

Area under the concentration-time curve from zero to a definite time [AUC(0-t)](Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study))
Area under the concentration-time curve from zero to 168 hours [AUC(0-168)](Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study))
Area under the concentration-time curve from zero to 24 hours(Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study))
Area under the concentration-time curve from zero to an infinite time [AUC(0-inf)](Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study))
Maximum plasma concentration [Cmax](Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study))
Minimum plasma concentration [Cmin](Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study))
Time to maximum plasma concentration [tmax](Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study))
Elimination half-life [t1/2](Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study))
Volume of distribution [Vz/F](Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study))
Clearance (CL/F)(Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study))
The number of Adverse Events (AE) that occurs(Adverse events will be recorded from informed consent through 30 days after the last dose of study drug)
Laboratory Parameters(Screening, Days 1, 8, and 15 of each treatment cycle (each cycle is 28 days))
The number of Serious Adverse Events (SAE) that occurs(SAEs will be recorded from the start of the first dose of AT-1965 (Cycle 1 Day 1) up to 30 days after the last dose of study drug or until resolution or stabilization of SAEs)
Clinical Benefit Ratio (CBR) based on RECISTv1.1 and iRECIST(3, 6 and 9 month)
Duration of Clinical Benefit (DoCB) based on RECISTv1.1 and iRECIST(3, 6 and 9 month)
Progression-free survival (PFS) based on RECIST version 1.1(3, 6 and 9 month)